The role of superspreading in Middle East respiratory syndrome coronavirus (MERS-CoV) transmission.

As at 15 June 2015, a large transmission cluster of Middle East respiratory syndrome coronavirus (MERSCoV)was ongoing in South Korea. To examine the potential for such events, we estimated the level of heterogeneity in MERS-CoV transmission by analyzing data on cluster size distributions. We found substantial potential for superspreading; even though it is likely that R0 < 1 overall, our analysis indicates that cluster sizes of over 150 cases are not unexpected forMERS-CoV infection.

Ebola virus disease outbreak in Nigeria: Transmission dynamics and rapid control.

International air travel has already spread Ebola virus disease (EVD) to major cities as part of the unprecedented epidemic that started in Guinea in December 2013. An infected airline passenger arrived in Nigeria on July 20, 2014 and caused an outbreak in Lagos and then Port Harcourt. After a total of 20 reported cases, including 8 deaths, Nigeria was declared EVD free on October 20, 2014. We quantified the impact of early control measures in preventing further spread of EVD in Nigeria and calculated the risk that a single undetected case will cause a new outbreak. We fitted an EVD transmission model to data from the outbreak in Nigeria and estimated the reproduction number of the index case at 9.0 (95% confidence interval [CI]: 5.2-15.6). We also found that the net reproduction number fell below unity 15 days (95% CI: 11-21 days) after the arrival of the index case. Hence, our study illustrates the time window for successful containment of EVD outbreaks caused by infected air travelers.

[Stopping secondary prevention in AIDS patients with inactive CMV retinitis treated with HAART (highly active antiretroviral therapy)]. / Absetzen der Sekundärprophylaxe bei Aids-Patienten mit inaktiver CMV-Retinitis unter HAART.

BACKGROUND: Immune recovery of AIDS patients with cytomegalovirus (CMV) retinitis treated and healed by highly active antiretroviral therapy (HAART) is reflected by increased CD4 cell count and decreased virus load. Due to partial reconstitution of the immune status the risk of opportunistic infections decreases, as well as the risk of reactivating inactive CMV retinitis. It may therefore be possible to stop anti-CMV maintenance therapy may after HAART-induced immune recovery. PATIENTS AND METHODS: We present six patients (nine eyes) with a follow-up of 9.5 months (range 7-12 months) after cessation of the CMV-specific maintenance therapy (five orally, one intravenously). RESULTS: There was no reactivation of retinal CMV infection during the follow-up period. The virus load (< 50 Eq/ml; a single value of one patient was 2047 Eq/ml) and CD4 cell counts (range 207-454/microliter; mean: 313/microliter) remained stable during the follow-up period, reflecting immune recovery. CONCLUSIONS: Our findings confirm the expected low risk of retinal CMV reactivation after immune recovery in AIDS patients receiving HAART without secondary prophylaxis with an anti-CMV maintenance therapy. Regular ophthalmic and medical follow-up is mandatory in these patients. Cessation of maintenance therapy represents a major improvement in quality of live in AIDS patients.

[Impression and applanation tonometry in irregular corneas. Comparison with intraocular needle tonometry]. / Impressions- und Applanationstonometrie bei pathologischen Hornhäuten. Vergleich mit der intraokularen Nadeldruckmessung.

PURPOSE: During the past 4 years we have demonstrated in eyes with corneal pathology that applanation tonometry (Goldmann, Perkins) generally delivers falsely low measurements in comparison to intraocular needle tonometry. The aim of this study was to evaluate whether impression tonometry (Schioetz) is more precise than applanation tonometry in determining the intraocular pressure in eyes with corneal disorders. PATIENTS AND METHODS: In 75 eyes with suspected glaucoma and various corneal disorders, we performed applanation tonometry and impression tonometry before intraocular needle tonometry. Applanation tonometry was repeated after impression tonometry to unveil a possible tonography effect. Intraocular needle tonometry was performed thereafter. RESULTS: Applanation tonometry results were 4.1 +/- 5.3 mmHg below intraocular pressure as determined by intraocular needle tonometry. Impression tonometry results were also lower: 4.3 +/- 6.8 mmHg (5.5 g), 4.3 +/- 6.4 mmHg (7.5 g), and 4.8 +/- 7.0 mmHg (10.0 g). The differences between applanation tonometry and impression tonometry were statistically not significant. In contrast, all the differences between extraocular tonometry procedures and intraocular needle tonometry were statistically highly significant (P < 0.001). CONCLUSION: In corneal pathology both, applanation tonometry and impression tonometry do not deliver reliable results on an average. Only intraocular needle-tonometry delivers reliable results in these eyes.

[Cyclosporin A therapy in severe anterior scleritis. 5 severe courses without verification of associated systemic disease treated with cyclosporin A]. / Ciclosporin-A-Therapie bei schweren anterioren Skleritiden. Fünf schwere Verläufe ohne nachgewiesene assoziierte Systemerkrankung unter systemischer Ciclosporin-A-Therapie.

BACKGROUND: Patients with severe scleritis who do not respond to high-dose corticosteroid therapy, or who require a daily corticosteroid maintenance dose higher than 30 mg prednisone should be treated by other immunosuppressants. PATIENTS AND METHODS: In five patients with various types of severe anterior scleritis a long-term high-dose steroid treatment failed to control scleral inflammation. They therefore received cyclosporin (CsA). Follow-up was 16-26 months. RESULTS: Scleral inflammation and ocular complications were controlled in all patients by a regimen of systemic CsA combined with a low maintenance steroid dose below the Cushing threshold. We observed no side effects under CsA serum levels of 120-150 ng/ml. In only one patient was scleral inflammation totally and lastingly eliminated. CONCLUSIONS: Systemic CsA therapy is of definite therapeutic value in the symptomatic management of steroid refractory severe anterior scleritis without associated systemic disease. Complete healing, however, is achieved only in a minority of cases.

Cloning and characterization of the breakpoint regions of a chromosome 11;18 translocation in a patient with hamartoma of the retinal pigment epithelium.

Mutations of various tumor suppressor genes, e.g., PTEN, TSC1, and TSC2, are known to be responsible for different inherited diseases presenting with multiple hamartomas, a benign tumor resembling neoplasia that results from faulty organ development. Combined hamartoma of the retinal pigment epithelium (RPE) and retina is a rare, congenital, focal malformation of the fundus. So far, no disease gene has been associated with this disorder. By molecular analysis of an apparently balanced and reciprocal translocation between the short arms of chromosomes 11 and 18, t(11;18)(p13;p11.31), in a patient with hamartoma of the RPE and retina, we selected PAC clones crossing the breakpoints on both derivative chromosomes 11 and 18. For the overlapping chromosome 11 clone, two EST clusters were identified, suggesting the existence of at least two genes in the breakpoint region. We constructed a PAC contig and showed that at least three exons of a novel gene map to the breakpoint region on chromosome 18. Based on the results of FISH analysis with the PAC clones of this contig, we suggest the occurrence of a complex rearrangement.

Cystoid macular edema following immune recovery and treatment with cidofovir for cytomegalovirus retinitis.

BACKGROUND: Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infection in AIDS patients. Cidofovir has proved to be highly effective in treatment of CMV retinitis. Iritis and bulbar hypotony are known as the major complications after intravenous and intravitreal use of this antiviral drug. Cystoid macular edema (CME) after intravenous application of cidofovir has not been reported. METHODS: We analyzed retrospectively the incidence of CME after intravitreal or intravenous application of cidofovir and its correlation with CD4 cell counts of the patients. RESULTS: Two (22.2%) of 9 eyes in the intravenous and 3 (18.8%) of 16 eyes in the intravitreal injection group developed CME. It occurred between 3 and 48 weeks after cidofovir administration. In all eyes CMV retinitis was inactive. All patients received highly active antiretroviral treatment (HAART). CME was correlated with a rapid and sustained improvement in CD4 cell counts. CONCLUSION: We interpret the occurrence of CME as an immune recovery phenomenon for the following reasons. All CMEs were seen in eyes with inactive CMV retinitis and the unaffected contralateral side never developed CME. The time range of appearance between 3 and 48 weeks after cidofovir administration makes direct toxicity of cidofovir unlikely. All patients had a sustained improvement of CD4 cell counts due to HAART. No CME was reported during the use of cidofovir before the HAART era.

Mycophenolate mofetil versus cyclosporin A in high risk keratoplasty patients: a prospectively randomised clinical trial.

BACKGROUND/AIMS: The requirement for an effective, minimally toxic immunosuppressive agent remains a major obstacle to performing high risk corneal transplantation. Although therapy with cyclosporin A (CSA) allows superior graft survival, its use is limited because of a wide range of side effects. Mycophenolate mofetil (MMF) has been shown to be a safe and effective immunosuppressive agent following renal transplantation. This prospective, randomised clinical trial was carried out to investigate the efficacy and safety of MMF in preventing corneal allograft rejection. METHODS: Recipients of corneal transplants who were at high risk for graft failure were randomly assigned to either CSA or MMF immunosuppressive therapy. CSA was given in doses to achieve whole blood trough levels of 120-150 ng/ml. MMF was given in a daily dose of 2 g. Both therapy groups additionally received oral corticosteroids (fluocortolone 1 mg/kg) which were tapered and discontinued within the first 3 postoperative weeks. Patients were monitored closely for evidence of corneal graft rejection and adverse side effects. Drug efficacy was measured, primarily, by the number of patients who experienced at least one episode of clinical graft rejection. Safety analysis focused on reported adverse side effects and laboratory measurements. RESULTS: 41 patients were enrolled in the study. There was no statistically significant difference between the two groups. 20 patients received CSA and 21 patients received MMF. Two patients in each group showed evidence of acute graft rejection which could be treated effectively by corticosteroids. All corneal grafts remained clear throughout the follow up. CONCLUSIONS: In this study it was shown that MMF is just as effective as CSA in preventing acute rejection following high risk corneal transplantation. Mycophenolate mofetil represents a promising alternative therapeutic option in patients who are at high risk for corneal graft failure.

[More than 4 years' experience with electronic intraocular needle tonometry]. / Mehr als vier Jahre Erfahrung mit der elektronischen intraokularen Nadel-Druckmessung bei irregulären Hornhäuten.

BACKGROUND: Applanation tonometry in eyes with pathological corneae can often not be performed or delivers rather questionable results. We report on our 4-year experience with electronic intraocular needle tonometry. PATIENTS AND METHODS: After since 1994 developing and calibrating a system for intraocular needle tonometry, we have performed 395 measurements in 252 eyes with irregular corneae and suspicion of glaucoma. If applanation tonometry values could be obtained, they were compared with the true intraocular pressure. RESULTS: Depending on the kind of corneal pathology, applanation tonometry values were lower and sometimes much lower than true intraocular pressure. No serious complications occurred as a result of intraocular needle tonometry. CONCLUSIONS: Intraocular needle tonometry is a safe procedure and is the only way to measure intraocular pressure precisely in eyes with pathological corneae.

Homologous penetrating central limbo-keratoplasty (HPCLK) in bilateral limbal stem cell insufficiency.

PURPOSE: Bilateral stem cell deficiency can be overcome only by keratoplasty plus additional homologous limbal transplantation. We have four years' experience with a new surgical one-stage procedure, homologous penetrating central limbo-keratoplasty (HPCLK). METHODS: A clinical trial was performed in order to evaluate the effectiveness of this new method. The first 25 eyes after HPCLK for limbal stem cell deficiency have been followed for more than 12 months. The eccentrically trephined unmatched grafts contained 40% limbus and were transplanted centrally in the host. Systemic cyclosporin A (CSA) was administered for at least one year. Central clear graft survival was the main outcome criterion. RESULTS: 18 grafts failed, mostly because of postoperative surface disorders. Seven grafts have remained centrally clear 12-41 months after HPCLK. CONCLUSIONS: In the majority of the grafts the transplanted limbal stem cells underwent immune destruction. The survival of seven grafts, however, shows that HPCLK is principally a promising new procedure. Further progress can be expected from the use of well HLA-matched grafts instead of unmatched grafts and from further improved systemic immune modulation.

[Intravitreal injection of cidofovir in cytomegalovirus retinitis]. / Intravitreale Injektion von Cidofovir bei CMV-Retinitis.

BACKGROUND: CMV retinitis is the most common opportunistic ocular infection and the main cause of blindness in AIDS patients with a T-helper cell count < or = 50/microliter. Cidofovir is a nucleotide analogue with a long half-life time after phosphorylation intracellularly. It is effective against CMV and can be given intravenously and intravitreally. The aim was to offer an alternative therapy for CMV retinitis to patients who could not receive standard treatment because of contraindications or refused it. The efficacy and tolerance of intravitreal injections of cidofovir should be evaluated. PATIENTS AND METHODS: We treated 16 eyes of 12 patients. The total number of injections with 15 micrograms of cidofovir each was 49, with an average of 3 injections per eye. The duration of follow-up was 75-295 days (median 170 days). Probenecid was given concomitantly. Injections were repeated after 6-10 weeks. Secondary prophylaxis of CMV organ infection was done with oral ganciclovir. RESULTS: Within a few days all areas with active retinitis turned into scars following the first injection. Under consequent treatment no reactivation was observed. Four eyes developed a mild iritis with hypotony within a mean time of 12 days after injection. All responded rapidly to topical steroids. None had a persisting loss of vision. Two eyes developed cystoid macular edema (CME). Two patients stopped anti-CMV treatment (ganciclovir orally and injections), followed by a recurrence after an average of 64-days. CONCLUSIONS: Intravitreal injection therapy with 15 micrograms cidofovir and concomitant oral probenecid is a valuable and safe alternative treatment for CMV retinitis in AIDS patients. Its main complication is iritis with hypotony, which is effectively treatable with topical steroids. No complications caused by the injection technique itself were noted. The occasional observation of CME in otherwise quiet eyes, however, is probably drug-related.

[Choroid infiltration in myelodysplastic syndrome]. / Choroidales Infiltrat auf dem Boden eines Myelodysplastischen Syndroms.

BACKGROUND: Myelodysplastic syndrome is a clonal disease of the hematopoetic system characterized by insufficiency of affected bone marrow cell lines. After long-term course of myelodysplastic syndrome an acceleration towards acute myeloic leukemia is a frequent finding. Involvement of the eye is a well known phenomenon in acute leukemia or in blast crisis with chronic leukemias. Eye involvement in myelodysplastic syndrome showing its transition into acute myeloic leukemia however has been published in only few cases. CASE REPORT: We present a 70-year-old male patient suffering from myelodysplastic syndrome, complaining of an acute visual decrease to 0.05 in the left eye. Clinical findings, ultrasound and fluoresceine angiography were in accordance with choroidal infiltration. From the hematologic findings, the myelodysplastic syndrome had been in partial remission after chemotherapy without any sign of relapse or exacerbation. Only because of the ophthalmologic diagnosis, bone marrow aspiration was performed and revealed progression of myelodysplastic syndrome to acute myeloic leukemia. Prompt administration of chemotherapy and external radiation of the posterior pol of the eye led to complete resolution of the fundus lesion within 10 days and visual acuity recovered to 0.8. CONCLUSION: To the best of our knowledge this is the first patient with a choroidal infiltration as the initial sign of progression of myelodysplastic syndrome to acute myeloic leukemia. Realizing this possibility helps for an early diagnosis and rapid therapy which is so crucial in prolonging life.

[Latanoprost (Xalatan)-induced macular edema]. / Latanoprost (Xalatan) induziertes Makulaödem.

BACKGROUND: Latanoprost represents a new therapeutic option in the treatment of chronic open angle glaucoma. It has only recently been reported for the first time that latanoprost caused cystoid macular edema in pseudophakic patients. CASE REPORT: A 60-year-old pseudophakic patient who suffered from a 10-year history of glaucoma, revealed a cystoid macular edema on fluorescence angiography after 10 days of treatment with latanoprost. One week after cessation of latanoprost therapy the cystoid edema in fluorescence angiography had resolved and the vision improved from 0.4 to 0.8. CONCLUSIONS: With respect to this severe complication, latanoprost should be used with great care and in clear indications, particularly in patients with risk of blood-aqueous leakage e.g. pseudophakic patients.

[Acute retinal necrosis syndrome. Argon laser coagulation for prevention of rhegmatogenic retinal detachment]. / Akutes Retinanekrose (ARN)-Syndrom. Argon-Laser-Koagulation (ALK) zur Prophylaxe rhegmatogener Netzhautablösungen.

BACKGROUND: ARN syndrome follows severeintraocular infection by herpes viruses and primarily affects the peripheral retina. Following scar formation, despite antiviral treatment, rhegmatogenous retinal detachment occurs very often. Prophylactic argon laser photocoagulation has therefore been proposed. We report our experience. PATIENTS: We treated five patients presenting clinically with advanced unilateral ARN with acyclovir. All eyes received a prophylactic confluent double row of argon laser treatment (500 microns, 0.2 s, gray-white lesions) central to the affected area as soon as was possible, depending on the vitreous clouding. Four patients were treated with Aspirin. RESULTS: One of the five patients had a peripheral rhegmatogenous retinal detachment that was limited by the argon laser row. Another patient had a tractional detachment needing vitreoretinal surgery. Two eyes developed vitreal hemorrhage of unknown origin. CONCLUSION: A lower rate of rhegmatogenous retinal detachments than expected occurred post-laser treatment. Vitreal hemorrhage was more frequent than previously reported. The bleeding probably originated from anterior retinal neovascularization and may have been enhanced by Aspirin treatment. We recommend early prophylactic argon laser photocoagulation in all ARN patients in agreement with the results of previous studies.

[Bilateral microsporidial keratitis in an HIV-positive patient with AIDS stage infection]. / Beidseitige Mikrosporidien-Keratitis bei einer HIV-positiven Patientin im Stadium AIDS.

INTRODUCTION: Microsporidia are spore-forming, obligate intracellular protozoa. Humans seem to be infected only by 4 genera of microsporidia. Microsporidial keratoconjunctivitis in immunodeficient patients has a characteristic appearance. CASE REPORT: 34 year old woman with AIDS complained of bilateral blurred vision. The visual acuity was 0.6 on both eyes. She had a mild conjunctivitis and disseminate, not very prominent intraepithelial corneal opacities. She was treated with propamidine isethionate 0.1% 5 times daily and artificial tears under presumptive diagnosis of microsporidial keratoconjunctivitis. We discontinued this treatment because of no improvement. Within 6 months the visual acuity decreased to 0.05. A conjunctival smear was positive for microsporidia. Local Fumagillin-eye-drops 0.07 mg/ml 7 times daily were given. Within 2 weeks an impressively improvement was seen. Because of an persisting diarrhea 400 mg Albendazol twice daily was added orally without success. DISCUSSION: The biomicroscopically changes of microsporidial keratoconjunctivitis are characteristical and lead to the clinical diagnosis. Fumagillin is in vitro and clinically a potent antimicrosporidian agent with an extremely broad therapeutic range.

Prophylactic argon laser coagulation for rhegmatogenous retinal detachment in AIDS patients with cytomegalovirus retinitis.

BACKGROUND: The incidence of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) reaches 20-45%. Despite aggressive medical treatment, rhegmatogenous retinal detachments develop in up to 30% of the affected eyes. Surgical repair is often difficult due to multiple large and hardly visible retinal holes with vitreal traction. Pars plana vitrectomy with instillation of silicone oil is the procedure of choice, giving limited functional results with anatomical reattachment. METHODS: We performed prophylactic laser coagulation in AIDS patients with medically treated CMV retinitis to prevent a progressive retinal detachment. Twenty-two quiescent CMV lesions in 22 eyes of 20 patients were treated with argon green laser coagulation. Each CMV lesion was completely surrounded with a double or triple row of laser spots (500-600 mumols; 0.2 s; gray-white lesions). RESULTS: The duration of follow-up was 2-24 months. Histopathologic evaluation was possible in two eyes of one patient. Reactivated or smoldering CMV retinitis crossed the laser scars in 11 eyes, making additional laser coagulation necessary. In four eyes retinal holes in the CMV scar tissue led to retinal detachment, which stopped at the laser scar. In three eyes the detachment is still controlled by the laser scar. In one eye, the detachment stopped at the laser scar for 6.5 months and then slowly progressed across it. There were no complications associated with our laser treatment. CONCLUSION: Prophylactic argon laser coagulation in quiescent CMV retinitis seems to reduce the rate of progressive retinal detachment with no need for vitrectomy and silicone oil tamponade.

[Mycophenolatemofetil in ocular immunological disorders. A survey of the literature with 3 case reports]. / Mycophenolatmofetil (CellCept) bei okulären immunologischen Störungen. Literaturübersicht mit 3 Kasuistiken.

BACKGROUND: Up to now ophthalmologists have only a small number of substances in their therapeutic armamentarium for the treatment of ocular immunological disorders. These are very potent agents, and any rapidly proliferating cells are extremely sensitive to such agents, thus the possibility of severe side effects is great. Mycophenolatemofetil (MMF) has been shown to be effective in preventing acute graft rejection following clinical renal and cardiac transplantation with a low risk of adverse events. Likewise MMF was effective in the treatment of experimental immunological disorders. A review of literature was performed in Medline. CASE REPORTS: We report on the effective use of MMF in a patient with ocular cicatricial pemphigoid, the switch from Cyclosporin A (CSA) therapy to MMF therapy following high-risk keratoplasty due to CSA allergy and about the combination therapy (CSA/MMF) in a patient following high risk keratoplasty, in whom CSA monotherapy was not sufficient to prevent allograft rejection. CONCLUSIONS: In these three cases MMF has been shown to be a safe and effective agent for the treatment of ocular immunological disorders. Whether these beneficial casuistic experiences will hold true will be depended on the outcome of longterm studies underway.